Air Pollution: A Silent Key Driver of Dementia

Abstract

In 2017, the Lancet Commission on Dementia Prevention, Intervention, and Care included air pollution in its list of potential risk factors for dementia; in 2018, the Lancet Commission on Pollution concluded that the evidence for a causal relationship between fine particulate matter (PM) and dementia is encouraging. However, few interventions exist to delay or prevent the onset of dementia. Air quality data are becoming increasingly available, and the science underlying the associated health effects is also evolving rapidly. Recent interest in this area has led to the publication of population-based cohort studies, but these studies have used different approaches to identify cases of dementia. The purpose of this article is to review recent evidence describing the association between exposure to air pollution and dementia with special emphasis on fine particulate matter of 2.5 microns or less. We also summarize here the proposed detailed mechanisms by which air pollutants reach the brain and activate the innate immune response. In addition, the article also provides a short overview of existing limitations in the treatment of dementia.

Keywords: air pollution; dementia; fine particulate matter; risk factors.

Figure 1

Current drugs approved for the treatment of cognitive impairment and AD-related dementia (registration and indication for oral and i.v. therapy). Abbreviations: AD—Alzheimer’s disease; i.v.—intravenous administration; Aβ—amyloid beta; NMDA—N-methyl-D-aspartate receptor; FDA—Food and Drug Administration (USA); EMA—European Medicines Agency (EMA); NMPA—National Medical Products Administration (China). * Continued approval will be based on further trials confirming a clinical benefit over currently available therapy.

Figure 2

Size-dependent regional deposition of inhaled particulate matters. The deposition sites of various inhaled particles of differing size (PM10, PM2.5, and PM1), which are located in specific regions of the respiratory tract. Created with BioRender.com (accessed on 3 February 2023).

Figure 3

Environmental exposures to air pollutants in the etiology and pathogenesis of dementia. Sources of air pollution (fine and ultrafine particles—UFPM) include particles smaller than 2.5 μm in diameter, for which annual average concentrations should not exceed 10 μg/m. Air pollution is a common environmental factor that affects the brain through multiple pathways (i.e., through the olfactory tract and blood vessels via the respiratory system). Particles affect the brain by accelerating (priming) microglia and astroglia and, thus, initiating neuroinflammation, production of reactive oxygen species (ROS), deposition of amyloid beta (Aβ) peptides, and tau phosphorylation. Aβ causes synaptic impairment, neuronal death, and progressive neurodegeneration, ultimately leading to Ad-related dementia and cognitive impairment. Created with BioRender.com (accessed on 12 May 2023).